Based on our previous findings of 1) asymmetrical regional and temporal functional development of cardiac sympathetic nerves (CSN) in puppies during the first six weeks of life and 2) decrease of ventricular fibrillation threshold (VFT) resulting from stimulation of individual CSN, as opposed to increased VFT associated with stimulation of stellate ganglia (SG) in older puppies, we hypothesize that autonomic maturational imbalance forms a basis for electrophysiologic imbalance and arrhythmiogenesis in early life. For this project period we propose 1) to continue the ongoing study on the effect of CSN maturation on the VFT in puppies one to six weeks of age. VFT will be tested in the control state and during selective stimulation and ablation of CSN and correlated with previous findings. 2) To study the functional development and the interaction of parasympathetic cardiac innervation with that of CSN in the first six weeks of life, using determinations of strength interval curves during parasympathetic and CSN stimulation or ablation. 3) To clarify whether or not findings obtained with CSN stimulation, such as age dependent differences in left to right sympathetic neural tone, in the first six weeks of life can be reflexly induced in response to hemodynamic manipulations, such as bilateral carotid artery or intermittent inferior vena cava occlusions to activate the sympathetics via the baroreceptor reflex, and 4) to clarify the role, if any, of developing alpha-adrenergic receptors in the documented CSN maturational changes and especially in the sympathetic regression observed in the third week. This will be assessed by refractory period changes in the control state and during stimulation of CSN before and after administration of an alpha-blocker in pups one to six weeks of age. Information from the above projects will further clarify the overall role of the autonomic nervous system and its maturational changes and interactions in cardiac electrophysiologic state and arrhythmiogenesis in early life.